For the past two decades RNA interference based technologies have offered an attractive potential approach for treating a variety of cancers where an 'oncogene' has been implicated in tumorigenesis. The current challenge to realizing the theoretical potential of siRNA efficacy is successful delivery. Head and neck squamous cell carcinomas (H&NSCC) are caused by tobacco and alcohol use, but recently an increasing percentage is recognized to be caused by HPV. E7 is the dominant HPV oncoprotein that is responsible for head and neck cancer which has a very poor prognosis. Although advances in surgery, radiation and conventional chemotherapy strategies for HNSCC are gradually improving outcomes, there is a clear unmet medical need for novel agents that can target the E7 oncogene.